The aim of this research is to study the immunoregulatory network in experimental autoimmune myasthenia gravis (EAMG) and in myasthenia gravis (MG), diseases in which the antigen, nicotinic acetylcholine receptor (AChR), is well defined. Such information may be applicable to other immunologically-based diseases in which the principle reaction is less well-understood. The idiotypic repertoire of the anti-AChR antibodies active in EAMG will be studied making use of rat monoclonal anti-AChR antibodies that have been prepared by means of hybridization of antibody-producing cells with myeloma cell lines. The fact that many of these monoclonal antibodies (mcabs) are capable of inducing EAMG when individually injected into normal animals makes it likely that some of these idiotypes (Ids) will be important in EAMG. Syngeneic animals will be immunized with anti-AChR mcabs to produce anti-idiotypic (anti-Id) serum and anti-Id mcabs. These anti-Id preparations will be used to search for the presence of Ids, and anti-Ids, in the serum and on the lymphocytes of both EAMG animals and patients with MG. Attempts will be made to modify the severity of EAMG by manipulating levels of important Ids by injection of anti-Id, either alone or in combination with cytotoxic drugs.